BrainAge modelling

A linear regression BrainAge model was trained for each cohort on e4 non-carriers and AB-. The model was then applied to the rest of the cohort.

The model was trained using the following features:

  • Amygdala normalized volume
  • Hippocampus normalized volume
  • Inferior parietal cortical thickness
  • Inferior temporal cortical thickness
  • Middle temporal cortical thickness
  • Entorhinal cortical thickness
  • Parahippocampal cortical thickness
  • Fusiform cortical thickness

A4/LEARN

Command used: model_age -o analysis/final/a4 -f data/final/a4/processed/structural_features.csv –clinical data/final/a4/processed/clinical.csv

## Cognitively Unimpaired
## Delta mean: 0.1307302
## Delta std: 1.897531

Delta differences

E4 status

Amyloid status

Sex differences

Biomarkers

Correlation between BrainAge delt and different biomarkers. Sensitivity analysis includes addin sex, educaiton, APOEe4, AB-status and MRI Age as covariates. Further sensitivity analysis limits datapoints to those within 1 year of the MRI.

PACC

## Sensitivity analysis:
## Correlation with delta including covariates: -0.1096922 9.226859e-06
## Correlation with delta including covariates and time difference: -0.1096922 9.226859e-06

AB

## Sensitivity analysis:
## Correlation with delta including covariates: 0.09647743 9.714027e-05
## Correlation with delta including covariates and time difference: 0.09677113 9.622892e-05

ptau217

## Sensitivity analysis:
## Correlation with delta including covariates: 0.252764 1.358219e-06
## Correlation with delta including covariates and time difference: 0.2507583 1.895654e-06

TAU

## Sensitivity analysis:
## Correlation with delta including covariates: 0.3885681 2.812268e-14
## Correlation with delta including covariates and time difference: 0.3883822 3.424027e-14

HABS

Command used: model_age -o analysis/final/habs -f data/final/habs/processed/structural_features.csv –clinical data/final/habs/processed/clinical.csv

## Cognitively Unimpaired
## Delta mean: 0.2680731
## Delta std: 4.290772

Delta differences

E4 status

Amyloid status

Sex differences

Biomarkers

Correlation between BrainAge delt and different biomarkers. Sensitivity analysis includes addin sex, educaiton, APOEe4, AB-status and MRI Age as covariates. Further sensitivity analysis limits datapoints to those within 1 year of the MRI.

PACC

## Sensitivity analysis:
## Correlation with delta including covariates: -0.08347256 0.1555244
## Correlation with delta including covariates and time difference: -0.1058491 0.08975296

AB

## Sensitivity analysis:
## Correlation with delta including covariates: 0.08023486 0.1722484
## Correlation with delta including covariates and time difference: 0.09757832 0.1019977

ptau217

## Sensitivity analysis:
## Correlation with delta including covariates: 0.1889458 0.008159636
## Correlation with delta including covariates and time difference: 0.1997575 0.006125103

TAU

## Sensitivity analysis:
## Correlation with delta including covariates: 0.172365 0.01597296
## Correlation with delta including covariates and time difference: 0.07228337 0.5671805

ADNI CU

Command used: model_age -o analysis/final/adni -f data/final/adni/processed/structural_features.csv –clinical data/final/adni/processed/clinical.csv

## Cognitively Unimpaired
## Delta mean: -0.2228206
## Delta std: 3.376072

Delta differences

E4 status

Amyloid status

Sex differences

Biomarkers

Correlation between BrainAge delt and different biomarkers. Sensitivity analysis includes addin sex, educaiton, APOEe4, AB-status and MRI Age as covariates. Further sensitivity analysis limits datapoints to those within 1 year of the MRI.

PACC

## Sensitivity analysis:
## Correlation with delta including covariates: -0.1394401 0.01015663
## Correlation with delta including covariates and time difference: -0.1394401 0.01015663

AB

## Sensitivity analysis:
## Correlation with delta including covariates: -0.02599843 0.6333661
## Correlation with delta including covariates and time difference: -0.07155647 0.2448108

ptau217

## Sensitivity analysis:
## Correlation with delta including covariates: -0.08520068 0.3276737
## Correlation with delta including covariates and time difference: 0.02875397 0.8244328

TAU

## Sensitivity analysis:
## Correlation with delta including covariates: 0.1123826 0.1960685
## Correlation with delta including covariates and time difference: 0.04844289 0.671598

ADNI MCI

## Mild Cognitive Impairment
## Delta mean: 1.63186
## Delta std: 3.782902

Delta differences

E4 status

Amyloid status

Sex differences

MCI vs CU

## Beta coefficient: 0.5409084
## Standard error: 0.08168485
## p-value: 3.54624e-11

Biomarkers

Correlation between BrainAge delt and different biomarkers. Sensitivity analysis includes addin sex, educaiton, APOEe4, AB-status and MRI Age as covariates. Further sensitivity analysis limits datapoints to those within 1 year of the MRI.

PACC

## Sensitivity analysis:
## Correlation with delta including covariates: -0.337818 2.109469e-12
## Correlation with delta including covariates and time difference: -0.337818 2.109469e-12

AB

## Sensitivity analysis:
## Correlation with delta including covariates: 0.2091212 1.965774e-05
## Correlation with delta including covariates and time difference: 0.2267829 2.427922e-05

ptau217

## Sensitivity analysis:
## Correlation with delta including covariates: 0.1435163 0.2161521
## Correlation with delta including covariates and time difference: -0.006040086 0.9742743

TAU

## Sensitivity analysis:
## Correlation with delta including covariates: 0.2152751 0.06182025
## Correlation with delta including covariates and time difference: 0.1070154 0.4642449

Meta-analysis

E4 status

## E4 All: 0.214262 ( 0.1225524 )
## E4 CU: 0.07981631 ( 0.4670774 )

AB status

## AB status All: 0.1647993 ( 0.2730926 )
## AB status CU: 0.08726586 ( 0.7060836 )

Sex

## Sex All: 0.2125713 ( 0.03616068 )
## Sex CU: 0.3098594 ( 0.06123631 )

PACC

## PACC All: -0.05269348 ( 0.4994625 )
## PACC CU: -0.03864339 ( 0.09065239 )

AB

## AB All: 0.1265149 ( 0.16919 )
## AB CU: 0.04986527 ( 0.6748085 )

pTau217

## pTau217 All: 0.1632234 ( 0.1537741 )
## pTau217 CU: 0.05712561 ( 0.7532778 )

Tau

## Tau All: 0.2453438 ( 0.06916416 )
## Tau CU: 0.1008083 ( 0.4161549 )

CU results

##    labels   estimates    ci_lower   ci_upper      pvals       i2        tau2
## 1 APOEe4+  0.07981631 -0.83452516 0.99415777 0.46707744  0.00000 0.000000000
## 2  Female  0.30985944 -0.07002528 0.68974416 0.06123631  0.00000 0.000000000
## 3    PACC -0.03864339 -0.10903801 0.03175124 0.09065239  0.00000 0.000000000
## 4  Aβ-PET  0.04986527 -1.08070800 1.18043853 0.67480850 63.98466 0.005065728
## 5 pTau217  0.05712561 -1.72107116 1.83532237 0.75327778 81.90014 0.016040537
## 6 Tau-PET  0.10080830 -0.88041884 1.08203544 0.41615488 36.66910 0.002187442

MCI results

##    labels  estimates    ci_lower   ci_upper        pvals
## 1 APOEe4+  0.5016849  0.29321053  0.7101593 2.397502e-06
## 2  Female  0.2907537  0.09473482  0.4867727 3.646138e-03
## 3    PACC -0.2379878 -0.31149208 -0.1644835 5.807488e-10
## 4  Aβ-PET  0.3085322  0.21035130  0.4067131 1.731692e-09
## 5 pTau217  0.2884503  0.10202679  0.4748739 3.266955e-03
## 6 Tau-PET  0.3508594  0.13109755  0.5706212 2.445951e-03